Fast-spiking (FS) interneurons are important elements of neocortical circuitry that constitute the primary source synaptic inhibition in adult cortex and impart temporal organization on ongoing cortical activity. The highly specialized intrinsic membrane firing properties allow FS to perform these functions attributable equally gene expression, which is ultimately coordinated by cell-type-specific transcriptional regulation. Although embryonic events govern initial steps cell-type...

Mutations in methyl-CpG-binding protein 2 (MeCP2) cause Rett syndrome and related autism spectrum disorders (Amir et al., 1999). MeCP2 is believed to be required for proper regulation of brain gene expression, but prior microarray studies <i>Mecp2</i> knock-out mice using tissue homogenates have revealed only subtle changes expression (Tudor 2002; Nuber 2005; Jordan 2007; Chahrour 2008). Here, by profiling discrete subtypes neurons we uncovered more dramatic effects on overcoming the...

Escalated aggression can have devastating societal consequences, yet underlying neurobiological mechanisms are poorly understood. Here, we show significantly increased inter-male mouse when neurotransmission is constitutively blocked from either of two subsets serotonergic, Pet1+ neurons: one identified by dopamine receptor D1(Drd1a)::cre-driven activity perinatally, and the other Drd2::cre pre-adolescence onward. Blocking neuron similar size and/or overlapping anatomical domains had no...

Among the brainstem raphe nuclei, dorsal nucleus (DR) contains greatest number of Pet1-lineage neurons, a predominantly serotonergic group distributed throughout DR subdomains. These neurons collectively regulate diverse physiology and behavior are often therapeutically targeted to treat affective disorders. Characterizing Pet1 neuron molecular heterogeneity relating it anatomy is vital for understanding functional organization, with potential inform therapeutic separability. Here we use...

Expression profiling of restricted neural populations using microarrays can facilitate neuronal classification and provide insight into the molecular bases cellular phenotypes. Due to formidable heterogeneity intermixed cell types that make up brain, isolating prior microarray processing poses steep technical challenges have been met in various ways. These methodological differences potential distort cell-type-specific gene expression profiles insofar as they may insufficiently filter out...

Sequencing of multiple mammalian genomes, together with the development whole-transcriptome profiling technologies, have opened door to an unprecedented ability study gene expression in brain. Transcriptomics refers a class high-throughput methods, such as microarray (gene chip

Significance Neuroanatomy is experiencing a renaissance due to the study of gene-expression data covering entire mouse brain and genome that have been recently released (the Allen Atlas). On other hand, some cell types extracted from characterized by their genetic activity. However, given type, it not known in which regions can be found. We propose computational model using Atlas solve this problem, thus estimating previously unidentified cell-type–specific maps brain. The used define through data.

Abstract Chronic traumatic encephalopathy (CTE) is a progressive tauopathy found in contact sport athletes, military veterans, and others exposed to repetitive head impacts. White matter rarefaction axonal loss have been reported CTE but not characterized on molecular or cellular level. Here, we present RNA sequencing profiles of cell nuclei from postmortem dorsolateral frontal white eight individuals with neuropathologically confirmed age- sex-matched controls. Analyzing these using...

Separation of the cortical sheet into functionally distinct regions is a hallmark neocortical organization. Cortical circuit function emerges from afferent and efferent connectivity, local connectivity within microcircuit, intrinsic membrane properties neurons that comprise circuit. While localization functions to particular areas can be partially accounted for by regional differences in both long range it unknown whether cell types differ between regions. Here we report first example...

Abstract The failure of chemoreflexes, arousal, and/or autoresuscitation to asphyxia may underlie some sudden infant death syndrome (SIDS) cases. In Part I, we showed that SIDS infants had altered 5-hydroxytryptamine (5-HT)2A/C receptor binding in medullary nuclei supporting and autoresuscitation. Here, using the same dataset, tested hypotheses prevalence low 5-HT1A 5-HT2A/C (defined as levels below 95% confidence interval controls—a new approach), percentages affected are greater versus...

The diverse cell types that comprise neocortical circuits each have characteristic integrative and firing properties are specialized to perform specific functions within the network. Parvalbumin-positive fast-spiking (FS) interneurons a particularly cortical cell-type controls dynamics of ongoing activity prevents runaway excitation by virtue remarkably high rates, feature is permitted narrow action potentials absence spike-frequency adaptation. Although several neuronal intrinsic membrane...

Synaptic scaling is a form of homeostatic plasticity driven by transcription-dependent changes in AMPA-type glutamate receptor (AMPAR) trafficking. To uncover the pathways involved, we performed cell-type-specific screen for transcripts persistently altered during scaling, which identified μ subunit (μ3A) adaptor protein complex AP-3A. increased μ3A (but not other AP-3 subunits) pyramidal neurons and redistributed dendritic AMPAR to recycling endosomes (REs). Knockdown prevented synaptic...

Abstract Vestibulospinal neurons are organized into discrete groups projecting from brainstem to spinal cord, enabling vertebrates maintain proper balance and posture. The two largest the lateral vestibulospinal tract (LVST) group contralateral medial (cMVST) group, with different projection lateralities functional roles. In search of a molecular basis for these differences, we performed RNA sequencing on LVST cMVST mouse chicken embryos followed by immunohistofluorescence validation....

The voxelized Allen Atlas of the adult mouse brain (at a resolution 200 microns) has been used in [arXiv:1303.0013] to estimate region-specificity 64 cell types whose transcriptional profile measured microarray experiments. In particular, model yields estimates for brain-wide density each these types. We conduct numerical experiments errors estimated profiles. First all, we check that simulated thalamic based on well-chosen genes can transfer signal from cerebellar Purkinje cells thalamus....

Abstract Chronic traumatic encephalopathy (CTE) is a progressive tauopathy found in contact sport athletes, military veterans, and others exposed to repetitive head impacts (RHI)1–6. White matter atrophy axonal loss have been reported CTE but not characterized on molecular or cellular level2,7,8. Here, we present RNA sequencing profiles of cell nuclei from postmortem dorsolateral frontal white eight individuals with neuropathologically confirmed age- sex-matched controls. Analyzing these...

SUMMARY Chronic traumatic encephalopathy (CTE) is a progressive tauopathy found in contact sport athletes, military veterans, and others exposed to repetitive head impacts (RHI) 1–6 . White matter atrophy axonal loss have been reported CTE but not characterized on molecular or cellular level 2,7,8 Here, we present RNA sequencing profiles of cell nuclei from postmortem dorsolateral frontal white eight individuals with neuropathologically confirmed age- sex-matched controls. Analyzing these...

Much of the genome is expressed in vertebrate brain, with individual genes exhibiting different spatially-varying patterns expression. These variations are not independent, pairs complex co-expression, such that two may be similarly one region, but differentially other regions. correlations have been previously studied quantitatively, particularly for gene expression atlas mouse biological meaning co-expression remains obscure. We propose a simple model terms spatial distributions underlying...

Abstract Among the brainstem raphe nuclei, dorsal nucleus (DR) contains greatest number of Pet1 -lineage neurons, a predominantly serotonergic group distributed throughout DR subdomains. These neurons collectively regulate diverse physiology and behavior are often therapeutically targeted to treat affective disorders. Characterizing neuron molecular heterogeneity relating it anatomy is vital for understanding functional organization, with potential inform therapeutic separability. Here we...